natriuretic-peptide--brain and Myocarditis

Due to the lack of prospective, randomized, controlled clinical studies on inflammation and cardiovascular involvement, the exact mechanism of cardiac injury among patients with Coronavirus Disease 2019 (COVID-19) still remains uncertain. It was demonstrated that there is a high and significantly positive linear correlation between troponin T and plasma high-sensitivity C-reactive protein levels, biomarkers of cardiac injury and systemic inflammation, respectively. Cardiac injury and inflammation is a relatively common association among patients hospitalized with COVID-19, and it is related to higher risk of in-hospital mortality. In our literature search, we identified several potential mechanisms of myocardial tissue damage, namely, coronavirus-associated acute myocarditis, angiotensin-converting enzyme 2 receptor binding affinity to the virus Spike protein, increased cytokine secretion, and hypoxia-induced cardiac myocyte apoptosis. Elucidation of the disease pathogenesis and prospective histopathological studies are crucial for future proper treatment in case of renewed outbreaks. Of interest is that with hundred of thousands of bodies available for autopsy studies, no prospective investigation has been reported so far. Strong efforts and continued research of the cardiovascular complications and identification of risk factors for poor prognosis in COVID-19 are steadily needed. The high morbidity and mortality of COVID-19, its monumental economic burden and social impact, the despair of a new pandemic outbreak, and the thread of potential utilization of novel severe acute respiratory syndrome coronavirus 2 as biologic weapons make it a preponderant necessity to better comprehend the therapeutic management of this lethal disease. Emerging as an acute infectious disease, COVID-19 may become a chronic epidemic because of genetic recombination. Therefore, we should be ready for the reemergence of COVID-19 or other coronaviruses.

Topics: Arrhythmias, Cardiac; Biomarkers; C-Reactive Protein; COVID-19; Cytokines; Hospitalization; Humans; Myocarditis; Natriuretic Peptide, Brain; Peptide Fragments; SARS-CoV-2; Troponin T

In our clinical practice, we recently found some patients with severe fulminant myocarditis (FM) who showed persistently elevated cardiac troponin (cTn) levels and "seemingly normal" B-type natriuretic peptide (BNP) level, and who subsequently progressed to poor outcomes. Indeed, this sounds contrary to conventional wisdom, but it is not an accidental phenomenon. Fulminant myocarditis is a rapidly progressive disease associated with high mortality. Recent studies have shown that patients with FM are significantly more likely to require heart transplantation than those without FM. Prompt diagnosis of FM and the institution of advanced cardiac life support will save more lives. Cardiac troponin and BNP are widely used diagnostic markers. Cardiac troponin is a specific marker of cardiac injury and its level correlates with the severity of cardiac injury. However, plasma BNP has a dual identity; it is not only a marker of cardiac pressure/volume overload, but it is also a cardioprotective factor that provides effective neurohormonal compensation to maintain homeostasis. Similar to fulminant hepatitis (characterised by diffuse inflammation and massive parenchymal cell necrosis) sometimes showing disproportion between transaminase level and bilirubin level, the disproportion between cTn and BNP levels in FM seems to be consistent with its severe histopathological changes, including diffuse infiltration of the myocardium by inflammatory cells, as well as severe cardiomyocyte injury and necrosis. Moreover, in previous studies, a lower BNP level was found to be an adverse prognostic marker in end-stage heart failure. All these findings indicate that in patients with FM with a persistently high cTn level and ominous clinical presentation, a "seemingly normal" BNP level is not a friendly signal. We hypothesise that the combination of a persistently elevated cTn level and low BNP level in patients with FM indicates worse myocardial injury and poor prognosis.

Topics: Biomarkers; Humans; Myocarditis; Natriuretic Peptide, Brain; Prognosis; Troponin

Giant cell myocarditis is a rare, often rapidly progressive and potentially fatal, disease due to T-cell lymphocyte-mediated inflammation of the myocardium that typically affects young and middle-aged adults. Frequently, the disease course is marked by acute heart failure, cardiogenic shock, intractable ventricular arrhythmias, and/or heart block. Diagnosis is often difficult due to its varied clinical presentation and overlap with other cardiovascular conditions. Although cardiac biomarkers and multimodality imaging are often used as initial diagnostic tests, endomyocardial biopsy is required for definitive diagnosis. Combination immunosuppressive therapy, along with guideline-directed medical therapy, has led to a paradigm shift in the management of giant cell myocarditis resulting in an improvement in overall and transplant-free survival. Early diagnosis and prompt management can decrease the risk of transplantation or death, which remain common in patients who present with cardiogenic shock.

Topics: Algorithms; Biomarkers; Biopsy; Cardiovascular Agents; Defibrillators, Implantable; Electrocardiography; Endocardium; Giant Cells; Heart; Heart Transplantation; Heart-Assist Devices; Humans; Immunosuppressive Agents; Myocarditis; Natriuretic Peptide, Brain; Troponin I

As the coronavirus disease 2019 (COVID-19) epidemic worsens, this global pandemic is impacting more than 200 countries/regions and more than 4,500,000 confirmed cases worldwide. COVID-19 is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which might attack not only the respiratory system, but also the other important organs, including the heart. It was reported that COVID-19 patients with a past history of cardiovascular diseases would have a higher mortality. Meanwhile, elevated troponin levels were frequently observed in COVID-19 cases. Besides the comprehensive treatments for COVID-19, as a cardiologist, we should also remain vigilant about the cardiac injuries, especially those with severe emergent cardiovascular symptoms.

Topics: Adult; Betacoronavirus; Biomarkers; Comorbidity; Coronary Disease; Coronavirus Infections; COVID-19; Humans; Interleukin-6; Male; Myocarditis; Natriuretic Peptide, Brain; Pandemics; Peptide Fragments; Pneumonia, Viral; Risk Factors; SARS-CoV-2; Treatment Outcome; Troponin I

The endocrine heart produces the polypeptide hormones Atrial Natriuretic Factor (ANF or ANP) and Brain Natriuretic Peptide (BNP). Through the peripheral actions of these hormones the heart contributes to the regulation of the cardiac preload and afterload. More recently, new functions for these hormones have been described including the modulation of the immune response. Plasma levels of BNP but not those of ANF, increase following an acute rejection episode of a cardiac allotransplant but return to levels pre-rejection with successful treatment. This observation constitutes the first observation leading to characterizing the interactions of BNP with the immune response. Several other pathologies with an inflammatory component are now known to be associated with an increase in the production of BNP. Such an increase is due to an increase in the transcriptional activity of the BNP gene induced by cytokines and related substances. In vitro investigations have shown that an increase in BNP directly modulates immunological activity. Inflammation and hemodynamic changes co-exist in several cardiovascular diseases and therefore it may be beneficial to measure circulating levels of both ANF and BNP as biomarkers of changes in intravascular volume and of changes in intravascular volume plus inflammation, respectively. Changes in plasma ANF, that are relatively larger than those of BNP, might be an indication of hemodynamic deterioration while important changes in circulating BNP could indicate a worsening of the inflammatory process.

Topics: Animals; Atrial Natriuretic Factor; Biomedical Research; Hemodynamics; Humans; Inflammation; Myocarditis; Myocytes, Cardiac; Natriuretic Peptide, Brain; Sepsis

Acute myocarditis is an inflammatory disease of the heart muscle that may progress to dilated cardiomyopathy and chronic heart failure. A number of factors including the sex hormone testosterone, components of innate immunity, and profibrotic cytokines have been identified in animal models as important pathogenic mechanisms that increase inflammation and susceptibility to chronic dilated cardiomyopathy. The clinical presentation of acute myocarditis is non-specific and mimics more common causes of heart failure and arrhythmias. Suspected myocarditis is currently confirmed using advanced non-invasive imaging and histopathologic examination of heart tissue. However, the diverse presentations of myocarditis and the lack of widely available, safe, and accurate non-invasive diagnostic tests remain major obstacles to early diagnosis and population based research. Recent advances in the understanding of disease pathogenesis described in this review should lead to more accurate diagnostic algorithms and non-invasive tests.

Topics: Algorithms; Animals; Biomarkers; Biopsy; Cardiomyopathy, Dilated; Diagnosis, Differential; Disease Progression; Early Diagnosis; Evidence-Based Medicine; Heart Failure; Humans; Inflammation; Myocarditis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Factors; Sex Distribution; Troponin I; Troponin T

Topics: Adverse Drug Reaction Reporting Systems; Aspirin; BNT162 Vaccine; C-Reactive Protein; COVID-19; Diuretics; Humans; Male; Middle Aged; Myocarditis; Natriuretic Peptide, Brain; RNA, Messenger; SARS-CoV-2; Vaccination

Although myocarditis following immune checkpoint inhibitor (ICI) therapy is rarely reported, it is considered clinically important because of its high mortality rate. Although various tests may be used for early diagnosis, abnormalities suggestive of myocarditis may not be detected. We report a case of ICI-induced myositis and concurrent asymptomatic myocarditis with mild cardiac marker elevation following nivolumab therapy in a 79-year-old man with metastatic gastric cancer. In this case, cardiac magnetic resonance imaging was useful for diagnosis. Treatment with oral prednisolone rapidly improved the patient's symptoms and creatine kinase levels. Follow-up examination revealed no flare-up of myositis and exacerbation of myocarditis. Since ICI-induced myositis is often complicated by myocarditis, this case report highlights the importance of detecting concurrent myocarditis in patients with ICI-induced myositis through intensive cardiac assessments to improve clinical outcomes.

Topics: Aged; Antineoplastic Agents, Immunological; Asymptomatic Diseases; Humans; Magnetic Resonance Imaging; Male; Myocarditis; Myositis; Natriuretic Peptide, Brain; Nivolumab; Peptide Fragments; Stomach Neoplasms; Troponin

The indications for immune checkpoint inhibitors (ICIs) are expanding in cancer drug therapy, and while cardiac events associated with ICIs are often fatal, there are few reports regarding cardiac complications associated with long-term ICI therapy. We aimed to study cardiac complications in patients undergoing long-term ICI therapy. From the database of our local cardio-oncology unit, we enrolled patients with cancer undergoing ICI therapy for more than 6 months and for whom cardiologists continuously performed routine follow-ups. We defined the primary endpoint as discontinuation of ICI due to cardiac events. We also analyzed changes in cardiac biomarkers and echocardiographic parameters. We retrospectively analyzed 55 consecutive patients (43 males, mean age: 65 ± 11 years) treated with ICI therapy in our hospital between January 2017 and June 2021. None of the patients discontinued ICI therapy due to cardiac events more than 6 months after treatment was initiated. Among the participants, we observed four patients with elevated serum troponin I levels, seven patients with decreased global longitudinal strain values, and two patients with elevated plasma brain natriuretic peptide levels. No patient required drug intervention for these cardiac events; furthermore, there were no cases of clinically diagnosed myocarditis. In the present study, there were no cardiac events causing ICI discontinuation in patients undergo ICI therapy for more than 6 months.

Topics: Aged; Antineoplastic Agents, Immunological; Biomarkers; Cardiotoxicity; Female; Humans; Immune Checkpoint Inhibitors; Male; Middle Aged; Myocarditis; Natriuretic Peptide, Brain; Retrospective Studies; Troponin I

Topics: Aged; Biomarkers; Female; Heart Failure; Humans; Male; Middle Aged; Myocarditis; Natriuretic Peptide, Brain; Prognosis; Retrospective Studies; Sarcoidosis; Stroke Volume; Ventricular Function, Left

Topics: Abdominal Pain; Acute Kidney Injury; Adolescent; Adult; Asthenia; Chest Pain; Conjunctivitis; Coronary Angiography; Coronary Care Units; COVID-19; Diarrhea; Dyspnea; Electrocardiography; Exanthema; Extracorporeal Membrane Oxygenation; Female; Fever; France; Headache; Humans; Hypotension; Intensive Care Units; Magnetic Resonance Imaging; Male; Mucocutaneous Lymph Node Syndrome; Myocarditis; Natriuretic Peptide, Brain; Peptide Fragments; Respiration, Artificial; SARS-CoV-2; Stroke Volume; Systemic Inflammatory Response Syndrome; Tachycardia; Troponin; Ventricular Dysfunction, Left; Young Adult

A four- and a half-month-old girl with severe dilated cardiomyopathy due to neonatal enterovirus myocarditis, treated with diuretics and milrinone for the past 4 months, was infected with SARS-CoV-2. The disease course was characterised by high fever and gastrointestinal symptoms. Cardiac function, as measured by echocardiography, remained stable. The treatment focused on maintaining a normal heart rate and a stable fluid balance. In children with severe underlying cardiac disease, even a mild SARS-CoV-2 infection can require close monitoring and compound treatment.

Topics: Cardiomyopathy, Dilated; Cardiotonic Agents; COVID-19; Diarrhea; Diuretics; Echocardiography; Enterovirus Infections; Female; Fever; Heart Rate; Heart Transplantation; Humans; Infant; Milrinone; Myocarditis; Natriuretic Peptide, Brain; Peptide Fragments; SARS-CoV-2; Severity of Illness Index; Tachycardia; Tachypnea; Troponin T; Ventricular Dysfunction, Left; Vomiting; Waiting Lists; Water-Electrolyte Balance

Geriatric patients with coronavirus disease (COVID-19) are at high risk of developing cardiac injury. Identifying the factors that affect high-sensitivity cardiac troponin I may indicate the cause of cardiac injury in elderly patients, and this could hopefully assist in protecting heart function in this patient population.. One hundred and eighty inpatients who were admitted for COVID-19 were screened. Patients older than 60 years were included in this study, and the clinical characteristics and laboratory results of the cohort were analyzed. The correlation between cardiac injury and clinical/laboratory variables was statistically analyzed, and further logistic regression was performed to determine how these variables influence cardiac injury in geriatric patients.. Age (p < 0.001) significantly correlated with cardiac injury, whereas sex (p = 0.372) and coexisting diseases did not. Rising procalcitonin (p = 0.001), interleukin-2 receptor (p < 0.001), interleukin 6 (p = 0.001), interleukin 10 (p < 0.001), tumor necrosis factor α (p = 0.001), high-sensitivity C-reactive protein (p = 0.001), D-dimer (p < 0.001), white blood cells (p < 0.001), neutrophils (p = 0.001), declining lymphocytes (p < 0.001), and natural killer cells (p = 0.005) were associated with cardiac injury and showed predictive ability in the multivariate logistic regression.. Our results suggest that age and inflammatory factors influence cardiac injury in elderly patients. Interfering with inflammation in this patient population may potentially confer cardiac protection.

Topics: Aged; Aged, 80 and over; Cardiomyopathies; COVID-19; Creatine Kinase; Humans; Inflammation Mediators; Killer Cells, Natural; L-Lactate Dehydrogenase; Male; Middle Aged; Myocarditis; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors; Troponin T

Here we present the case of a 37-year-old previously healthy man who developed fever, headache and a unilateral, painful neck swelling while working offshore. He had no known contact with anyone with COVID-19; however, due to the ongoing pandemic, a nasopharyngeal swab was performed, which was positive for the virus. After transfer to hospital for assessment his condition rapidly deteriorated, requiring admission to intensive care for COVID-19 myocarditis. One week after discharge he re-presented with unilateral facial nerve palsy. Our case highlights an atypical presentation of COVID-19 and the multifaceted clinical course of this still poorly understood disease.

Topics: Adult; Alkalosis, Respiratory; Bell Palsy; Blood Gas Analysis; C-Reactive Protein; COVID-19; Echocardiography; Edema; Electrocardiography; Humans; Hypotension; Lymphadenitis; Magnetic Resonance Imaging; Male; Myocarditis; Natriuretic Peptide, Brain; Neck; Oxygen Inhalation Therapy; Peptide Fragments; Procalcitonin; Recovery of Function; SARS-CoV-2; Troponin T; Vasoconstrictor Agents

Topics: Autoimmune Diseases; CD8-Positive T-Lymphocytes; Dermatitis; Diarrhea; Echocardiography; Female; Glucocorticoids; Humans; Immune Checkpoint Inhibitors; Immunoglobulins, Intravenous; Immunologic Factors; Ipilimumab; Lymph Nodes; Lymphatic Metastasis; Magnetic Resonance Imaging; Melanoma; Middle Aged; Myocarditis; Natriuretic Peptide, Brain; Nivolumab; Skin Neoplasms; Telemetry; Thyroiditis; Troponin I

Topics: Atrioventricular Block; Biopsy; Cardiomyopathies; Diagnosis, Differential; Disease Progression; Echocardiography; Fluorodeoxyglucose F18; Giant Cells; Granuloma; Heart Block; Heart Failure; Heart Transplantation; Humans; Lymph Nodes; Magnetic Resonance Imaging; Male; Middle Aged; Myocarditis; Myocardium; Natriuretic Peptide, Brain; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Sarcoidosis; Stroke Volume; Troponin I

A 17-year-old obese male was admitted to the pediatric intensive care unit after presenting with fluid-responsive septic shock following 7 days of fever, gastrointestinal symptoms and neck pain. Initial workup was positive for SARS-CoV-2 and elevated troponin I and brain natriuretic peptide. Echocardiography and cardiac magnetic resonance imaging confirmed acute myocarditis. One week after discharge, repeat echocardiogram demonstrated improved heart function with only residual myocardial dysfunction.

Topics: Adolescent; Betacoronavirus; Coronavirus Infections; COVID-19; Echocardiography; Heart; Humans; Intensive Care Units; Magnetic Resonance Imaging; Male; Myocarditis; Natriuretic Peptide, Brain; New York City; Pandemics; Pneumonia, Viral; SARS-CoV-2; Shock, Septic

Topics: Adult; Aged; Autopsy; Betacoronavirus; Biomarkers; Cardiovascular Diseases; Cell Death; Comorbidity; Coronavirus Infections; COVID-19; Diabetes Mellitus; Endothelium; Female; Heart; Humans; Lymphopenia; Male; Microscopy, Electron; Middle Aged; Muscle Cells; Myocarditis; Myocardium; Natriuretic Peptide, Brain; Obesity; Pandemics; Pneumonia, Viral; Renal Insufficiency, Chronic; SARS-CoV-2; Troponin I

Topics: Adolescent; Adult; Asymptomatic Infections; Betacoronavirus; C-Reactive Protein; Chest Pain; Coronavirus Infections; COVID-19; Edema; Female; Ferritins; Fibrin Fibrinogen Degradation Products; Humans; Magnetic Resonance Imaging; Magnetic Resonance Imaging, Cine; Male; Myocarditis; Natriuretic Peptide, Brain; Pandemics; Pneumonia, Viral; Pregnancy; Pregnancy Complications, Infectious; Puerperal Disorders; SARS-CoV-2; Troponin I; Troponin T

We describe the presentation, treatment and outcome of children with multisystem inflammatory syndrome with COVID-19 (MIS-C) in Mumbai metropolitan area in India.. This is an observational study conducted at four tertiary hospitals in Mumbai. Parameters including demographics, symptomatology, laboratory markers, medications and outcome were obtained from patient hospital records and analyzed in patients treated for MIS-C (as per WHO criteria) from 1 May, 2020 to 15 July, 2020.. 23 patients (11 males) with median (range) age of 7.2 (0.8-14) years were included. COVID-19 RT-PCR or antibody was positive in 39.1% and 30.4%, respectively; 34.8% had a positive contact. 65% patients presented in shock; these children had a higher age (P=0.05), and significantly higher incidence of myocarditis with elevated troponin, NT pro BNP and left ventri-cular dysfunction, along with significant neutrophilia and lympho-penia, as compared to those without shock. Coronary artery dilation was seen in 26% patients overall. Steroids were used most commonly for treatment (96%), usually along with intra-venous immunoglobulin (IVIg) (65%). Outcome was good with only one death.. Initial data on MIS-C from India is presented. Further studies and longer surveillance of patients with MIS-C are required to improve our diagnostic, treatment and surveillance criteria.

Topics: Adolescent; Biomarkers; Child; Child, Preschool; COVID-19; Female; Glucocorticoids; Humans; Immunoglobulins, Intravenous; India; Infant; Lymphopenia; Male; Myocarditis; Natriuretic Peptide, Brain; Neutrophils; Peptide Fragments; Shock; Systemic Inflammatory Response Syndrome; Troponin; Ventricular Dysfunction, Left

This case aims to remind all providers to scrutinise for atypical presentations of multisystem inflammatory syndrome in children (MIS-C) which may mimic a more routine diagnosis. In the absence of mucocutaneous symptoms, the diagnosis of MIS-C can be missed. Given the potential for rapid deterioration of patients with MIS-C, early treatment and inpatient interventions are necessary.

Topics: Abdominal Pain; Adenosine Monophosphate; Alanine; C-Reactive Protein; Child; COVID-19; COVID-19 Drug Treatment; COVID-19 Nucleic Acid Testing; COVID-19 Serological Testing; Diagnosis, Differential; Fever; Humans; Interleukin 1 Receptor Antagonist Protein; Intubation, Intratracheal; Male; Mucocutaneous Lymph Node Syndrome; Myocarditis; Nasopharynx; Natriuretic Peptide, Brain; SARS-CoV-2; Systemic Inflammatory Response Syndrome; Tachycardia; Treatment Outcome

Mesalazine (5-aminosalicylic acid)-based products are a widely used treatment for inflammatory bowel disease in children and adults. Associated myopericarditis is an uncommon but recorded phenomenon related to drug hypersensitivity. Unless recognised, this important complication may culminate in the development of dilated cardiomyopathy and severe heart failure. We report the case of a boy with Crohn's disease who developed myopericarditis 14 days after starting treatment with mesalazine. Discontinuation of the drug rapidly led to normalisation of left ventricular structure and function, and a parallel improvement in the levels of plasma N-terminal pro-B-type natriuretic peptide and other markers of myocardial damage. Clinicians should be aware of this potentially life-threatening adverse effect of mesalazine therapy, which is quickly and fully reversible on cessation of the agent.

Topics: Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Crohn Disease; Diagnosis, Differential; Humans; Male; Mesalamine; Myocarditis; Natriuretic Peptide, Brain; Peptide Fragments

Kawasaki disease (KD) vasculitis is an acute febrile illness of childhood characterized by systemic vasculitis of unknown origin, and is the most common cause of acquired heart disease among children in the United States. While  histological evidence of myocarditis can be found in all patients with acute KD, only a minority of patients are clinically symptomatic and a subset demonstrate echocardiographic evidence of impaired myocardial function, as well as increased left ventricular mass, presumed to be due to myocardial edema and inflammation. Up to a third of KD patients fail to respond to first-line therapy with intravenous immunoglobulin (IVIG), and the use of interleukin (IL)-1 receptor antagonist (IL-1Ra, anakinra) is currently being investigated as an alternative therapeutic approach to treat IVIG-resistant patients. In this study, we sought to investigate the effect of IL-1Ra on myocardial dysfunction and its relation to myocarditis development during KD vasculitis. We used the Lactobacillus casei cell-wall extract (LCWE)-induced murine model of KD vasculitis and investigated the effect of IL-1Ra pretreatment on myocardial dysfunction during KD vasculitis by performing histological, magnetic resonance imaging (MRI) and echocardiographic evaluations. IL-1Ra pretreatment significantly reduced KD-induced myocardial inflammation and N-terminal pro B-type natriuretic peptide (NT-proBNP) release. Both MRI and echocardiographic studies on LCWE-injected KD mice demonstrated that IL-1Ra pretreatment results in an improved ejection fraction and a normalized left ventricular function. These findings further support the potential beneficial effects of IL-1Ra therapy in preventing the cardiovascular complications in acute KD patients, including the myocarditis and myocardial dysfunction associated with acute KD.

Topics: Animals; Cardiomyopathies; Disease Models, Animal; Immunoglobulins, Intravenous; Inflammation; Interleukin 1 Receptor Antagonist Protein; Lacticaseibacillus casei; Male; Mice; Mice, Inbred C57BL; Mucocutaneous Lymph Node Syndrome; Myocarditis; Natriuretic Peptide, Brain; Receptors, Interleukin-1; Vasculitis

The ever-increasing use of immune checkpoint inhibitors in cancer is leading to a high incidence of autoimmune side effects. This report discusses an autoimmune fulminant myocarditis in an elderly patient with metastatic pulmonary adenocarcinoma in whom the most advanced invasive heart failure therapies were used successfully. She was treated with nivolumab. This case illustrates a severe cardiovascular complication of immunotherapy and highlights to cardiologists the importance of aggressive treatments in patients with metastatic cancers whose prognosis has improved dramatically.

Topics: Adenocarcinoma of Lung; Aged; Antineoplastic Agents; Edema; Female; Heart Failure; Humans; Myocarditis; Natriuretic Peptide, Brain; Nivolumab; Peptide Fragments; Shock, Cardiogenic; Troponin

There is often a diagnostic dilemma in pediatric patients presenting with depressed ventricular function, as myocarditis and dilated cardiomyopathy (DCM) of other etiologies can appear very similar. Accurate identification is critical to guide treatment and to provide families with the most accurate expectation of long-term outcomes. The objective of this study was to identify patterns of clinical presentation and to assess non-invasive measures to differentiate patients with acute myocarditis from other forms of DCM. We identified all children (< 18 years) from our institution with a diagnosis of idiopathic DCM or myocarditis based on endomyocardial biopsy or explant pathology (1996-2015). Characteristics at the time of presentation were compared between patients with a definite diagnosis of myocarditis and those with idiopathic DCM. Data collected included clinical and laboratory data, radiography, echocardiography, and cardiac catheterization data. A total of 58 patients were included in the study; 46 (79%) with idiopathic DCM and 12 (21%) with acute myocarditis. Findings favoring a diagnosis of myocarditis included a history of fever (58 vs. 15%, p = 0.002), arrhythmia (17 vs. 0%, p = 0.003), higher degree of cardiac enzyme elevation, absence of left ventricular dilation (42 vs. 7%, p = 0.002), segmental wall motion abnormalities (58 vs. 13%, p = 0.001), lower left ventricular dimension z-score (3.7 vs. 5.2, p = 0.031), and less severe depression of left ventricular systolic function. There are notable differences between patients with myocarditis and other forms of DCM that can be detected non-invasively at the time of presentation without the need for endomyocardial biopsy. These data suggest that it may be possible to develop a predictive model to differentiate myocarditis from other forms of DCM using non-invasive measures.

Topics: Adolescent; Arrhythmias, Cardiac; Biomarkers; Biopsy; Cardiac Catheterization; Cardiomyopathy, Dilated; Child; Child, Preschool; Diagnosis, Differential; Echocardiography; Female; Heart; Humans; Infant; Male; Myocarditis; Myocardium; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

A clinical course ranging from mild local findings to life-threatening systemic findings may occur after scorpion stings. The purpose of this study was to identify priority markers indicating scorpion sting-related cardiac involvement.. Our study was performed between July 2014, and September 2015 in the Çukurova University medical faculty pediatric emergency department, in Adana, Turkey. Patients admitted with scorpion sting-related cardiac involvement and a control group consisting of patients with no scorpion sting-related cardiac involvement were included in the study. Troponin I at time of presentation and at 6 and 24 h, N-terminal prohormone of brain natriuretic peptide (NTproBNP), ejection fraction as determined by echocardiography at 24 h, and peak and end of T wave (Tp-e) and Tp-e/QTc ratios with echocardiography at 24 h were evaluated.. A patient group consisting of 7 cases of scorpion envenomation-related myocarditis and a control group of 30 cases of scorpion intoxication without myocarditis findings were enrolled. Statistically significantly high glucose, white blood cell values, creatine kinase MB, troponin I, and NTproBNP values were identified in the scorpion sting-related myocarditis group (P<0.05). Ejection fractions determined by echocardiography at time of presentation were significantly lower in the patients with myocarditis compared with the control group (P<0.05). A statistically significant difference was identified between Tp-e/corrected QT interval (QTc) ratios investigated in DI and V2 derivations in patient and control group echocardiograms (P<0.05).. We think that use can be made of NTproBNP in addition to echocardiography and troponin I in the early diagnosis of scorpion sting-related myocarditis and that Tp-e and Tp-e/QTc ratios identified via echocardiography can be used as early markers; however, further studies with larger numbers are needed to confirm this.

Topics: Adolescent; Child; Child, Preschool; Early Diagnosis; Echocardiography; Female; Humans; Infant; Male; Myocarditis; Natriuretic Peptide, Brain; Peptide Fragments; Scorpion Stings; Troponin I; Turkey

Metformin is a widely used anti-diabetic drug and increasing evidence suggests that metformin have profound cardioprotective effects under both diabetic and non-diabetic situations. The protective benefits of metformin have been proved in diabetic patients with cardiovascular complications and in experimental animals with myocardial infarction and cardiac hypertrophy. In the present study, we found that treatment with metformin inhibited the cardiac expression of pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and interleukin 6 (IL-6) in endotoxin-challenged mice. Treatment with metformin also alleviated the histological abnormalities in the heart, suppressed the upregulation of myeloperoxidase (MPO), decreased the elevation of creatinine kinase-myocardial band (CK-MB) and brain natriuretic peptide (BNP). Treatment with metformin promoted the phosphorylation of the catalytic α subunit of adenosine 5'-monophosphate-activated protein kinase (AMPKα), co-administration of AMPK inhibitor suppressed the stimulatory effects of metformin on AMPKα phosphorylation. Meanwhile, the suppressive effects of metformin on MPO, TNF-α, CK-MB and BNP were reversed by the AMPK inhibitor. On the contrary, administration of AMPK activator mimicked the effects of metformin on AMPKα phosphorylation, MPO upregulation, CK-MB release and BNP elevation. These evidence suggested that metformin might provide beneficial effects in endotoxin-induced acute myocarditis via activating AMPK-dependent anti-inflammatory mechanism.

Topics: Acute Disease; AMP-Activated Protein Kinases; Animals; Anti-Inflammatory Agents; Cytokines; Heart; Humans; Inflammation Mediators; Lipopolysaccharides; Male; Metformin; Mice; Mice, Inbred BALB C; Myocarditis; Myocardium; Natriuretic Peptide, Brain; Peroxidase

To investigate the changes in serum cardiac myosin light chain 1 (CMLC-1) levels in children with fulminant myocarditis (FM) during continuous blood purification (CBP), as well as to analyze its correlation with other laboratory indexes.. Twenty-four (24) children with FM who underwent CBP were enrolled. Before and during treatment (48 and 72 hours after treatment, or death), the optical density value of serum CMLC-1 was measured using enzyme-linked immunosorbent assay, and then the serum CMLC-1 concentration was calculated. The correlations between CMLC-1 OD value change and laboratory indexes including creatine kinase-MB (CK-MB), troponin, myohemoglobin and N-terminal pro-brain natriuretic peptide (NT-proBNP) were analyzed.. The serum CMLC-1 concentration significantly increased in the children with FM and decreased obviously during CBP therapy. In the same period, the change of CMLC-1 concentration were positively correlated with creatine kinase-MB (r=0.528), troponin (r=0.726), myohemoglobin (r=0.702), and NT-proBNP levels (r=0.589).. The serum CMLC-1 concentration increases significantly in children with FM, but CBP therapy can effectively control this increase.

Topics: Biomarkers; Child; Creatine Kinase, MB Form; Enzyme-Linked Immunosorbent Assay; Hemofiltration; Humans; Myocarditis; Myoglobin; Myosin Light Chains; Natriuretic Peptide, Brain; Peptide Fragments; Reference Values; Statistics, Nonparametric; Time Factors; Troponin

Myocardial dysfunction and heart failure (HF) are increased in rheumatoid arthritis (RA), yet there are few studies of the myocardium in RA.. RA patients with no known heart disease or risk factors underwent gadolinium-enhanced cardiac magnetic resonance imaging (MRI). Images were assessed for left-ventricular (LV) structural and functional parameters and for myocardial late gadolinium enhancement (LGE; an indicator of myocardial fibrosis) and T2-weighted imaging (an indicator of active inflammation). We modeled the associations between RA characteristics and N-terminal pro-brain natriuretic protein (NT-proBNP) levels with LGE and T2-weighted imaging. We also assessed whether LGE and/or T2-weighted imaging were associated with abnormal LV structure or dysfunction.. A total of 60 RA patients were studied. LGE was present in 19 (32%) and T2-weighted imaging in 7 (12%), 5 of whom also had LGE. After adjustment for relevant confounders, higher odds of LGE with each swollen joint (odds ratio [OR] 1.87, P = 0.008), each log unit higher C-reactive protein level (OR 3.36, P = 0.047), and each log unit higher NT-proBNP (OR 20.61, P = 0.009) were found. NT-proBNP was also significantly higher (135%) among those with T2-weighted imaging than in those without T2-weighted imaging or LGE. Higher LV mass index and LV mass:end diastolic volume ratio were observed in those with T2-weighted imaging than in those with no myocardial abnormalities and in those with LGE without T2-weighted imaging; however, ejection fraction was not reduced in those with either LGE or T2-weighted imaging.. These data suggest that cardiac MRI findings indicating myocardial inflammation/fibrosis are correlated with RA disease activity and alterations in myocardial structure known to precede clinical HF.

Topics: Adult; Aged; Arthritis, Rheumatoid; C-Reactive Protein; Contrast Media; Endomyocardial Fibrosis; Female; Gadolinium DTPA; Heart; Humans; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Myocarditis; Myocardium; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Risk Factors

Patients with myocarditis and left ventricular (LV) dysfunction may improve after standard heart failure therapy. This improvement seems to be related to retreat of myocardial inflammation. The aim of the present study was to assess changes in clinical, echocardiographic and some laboratory parameters and to correlate them with changes in the number of inflammatory infiltrating cells in endomyocardial biopsy (EMB) samples during the 6-month follow-up, and to define predictors of LV function improvement among baseline parameters. Forty patients with biopsy-proven myocarditis and impaired LV function (LV ejection fraction-LVEF <40 %) with heart failure symptoms ≤ 6 months were evaluated. Myocarditis was defined as the presence of >14 mononuclear leukocytes/mm(2) and/or >7 T-lymphocytes/mm(2) in the baseline EMB. The EMB, echocardiography and clinical evaluation were repeated after 6 months of standard heart failure therapy. LVEF improved on average from 25 ± 9 to 42 ± 12 % (p < 0.001); LV end-systolic volume and LV end-diastolic volume (LVEDV) decreased from 158 ± 61 to 111 ± 58 ml and from 211 ± 69 to 178 ± 63 ml (both p < 0.001). NYHA class decreased from 2.6 ± 0.5 to 1.6 ± 0.6 (p < 0.001) and NTproBNP from 2892 ± 3227 to 851 ± 1835 µg/ml (p < 0.001). A decrease in the number of infiltrating leukocytes (CD45+/LCA+) from 23 ± 15 to 13 ± 8 cells/mm(2) and in the number of infiltrating T lymphocytes (CD3+) from 7 ± 5 to 4 ± 3 cells/mm(2) (both p < 0.001) was observed. The decline in the number of infiltrating CD45+ cells significantly correlated with the change in LVEF (R = -0.43; p = 0.006), LVEDV (R = 0.39; p = 0.012), NYHA classification (R = 0.35; p = 0.025), and NTproBNP (R = 0.33; p = 0.045). The decrease in the number of CD3+ cells correlated with the change of systolic and diastolic diameters of the left ventricle (R = -0.33; p = 0.038 and R = -0.45; p = 0.003) and with the change in LVEDV (R = -0.43; p = 0.006). Tricuspid annular plane systolic excursion (TAPSE) (OR 0.61; p = 0.005) and early transmitral diastolic flow velocity (E wave) (OR 0.89; p = 0.002) were identified as predictors of LVEF improvement. Improvements in clinical status, LV function and NTproBNP levels correlated with decrease in the number of infiltrating inflammatory cells. TAPSE and E wave velocity were significant predictors of improvement in multivariate regression. Our observations suggest that contemporary guidelines-based therapy of heart failure is an effective treatment

Topics: Adult; Biomarkers; Biopsy; Cardiomyopathies; Cardiovascular Agents; Chemotaxis, Leukocyte; Echocardiography, Doppler; Female; Heart Failure; Humans; Male; Middle Aged; Multivariate Analysis; Myocarditis; Myocardium; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Predictive Value of Tests; Recovery of Function; Risk Factors; Stroke Volume; T-Lymphocytes; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

To detect the relationship of N-terminal pro-brain natriuretic peptide levels with clinical and laboratory findings by measuring them at diagnosis, during, and after treatment in children with acute rheumatic carditis.. A total of 40 children including 20 acute rheumatic carditis patients aged between 5 and 16 years 20 healthy children as controls were included in the study. Blood was drawn from patients at diagnosis and in the first week, first month and third month after treatment in order to detect pro-brain natriuretic peptide, C-reactive protein levels and erythrocyte sedimentation rates. All patients underwent echocardiography.. The N-terminal pro-brain natriuretic peptide levels of children with acute rheumatic carditis were significantly higher than those of the control group at diagnosis and during treatment (p<0.05). Echocardiographic evaluation of acute rheumatic carditis patients revealed that the left atrium diameter continued to decrease during the study and that the mean left atrium diameters measured at diagnosis and in the first week were statistically higher than the mean left atrium diameters measured in the third month. There was significant correlation between left atrium diameters at diagnosis and in the first month and N-terminal pro-brain natriuretic peptide levels during the same periods in the patient group.. Previous studies have used N-terminal pro-brain natriuretic peptide levels as a marker of enlargement of the left atrium, whereas in this study we want to emphasise its role as a marker of inflammation. This increase was significantly correlated with enlargement in the left atrium. N-terminal pro-brain natriuretic peptide levels were found to be a valuable determinant in indicating cardiac inflammation and haemodynamics.

Topics: Acute Disease; Adolescent; Biomarkers; Child; Child, Preschool; Echocardiography, Doppler, Color; Female; Heart Ventricles; Humans; Male; Monitoring, Physiologic; Myocarditis; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Protein Precursors; Rheumatic Heart Disease; Ventricular Function

Dilated cardiomyopathy is a leading cause of cardiac death in children. Approximately 30% of children die or need cardiac transplantation in the first year after establishing the diagnosis. New strategies are needed to improve the outcome in this high-risk patient population.. We present our experience in 38 patients below the age of three years, who were diagnosed with dilated cardiomyopathy and who were treated at our institution between 2006 and 2012. The treatment strategy involved institution of β-blockers and angiotensin-converting enzyme inhibitors as soon as feasible. In selected cases, pulmonary artery banding or intracoronary autologous bone marrow-derived cell therapy was performed. The median age at presentation was six months (range 1-26 months). The median follow-up age was 16 months (range 2-80 months). Kaplan-Meier analysis of survival after dilated cardiomyopathy diagnosis revealed a one-year survival of 97% and a five-year survival of 86%. The rate of freedom from death or heart transplantation was 82% at one year and 69% at five years. Surviving patients who were free of transplantation, at the follow-up at 25 months (3-80 months), showed a significant improvement in left ventricular ejection fraction (from 19±11 to 46±16%) and left ventricular end-diastolic diameter (z-score from 4.6±2.4 to 1.4±1.6). In addition, the levels of B-type natriuretic peptide improved significantly (from 3330±3840 to 171±825 pg/ml).. Our data suggest that the clinical approach described here may result in a markedly improved medium-term outcome in young children with dilated cardiomyopathy. Further studies are required to evaluate whether these approaches reduce end-points such as transplantation or death.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiomyopathy, Dilated; Child, Preschool; Female; Follow-Up Studies; Heart Failure; Heart Transplantation; Humans; Infant; Kaplan-Meier Estimate; Male; Myocarditis; Natriuretic Peptide, Brain; Stroke Volume; Ventricular Function, Left

Desmin regulates function of mitochondria, T-tubular system and cytosolic Ca(2+) transients. We investigated whether desmin remodeling correlates with diastolic dysfunction and whether progressive desmin abnormalities are accompanied by increasing diastolic dysfunction stages.. Eighty five patients with idiopathic dilated cardiomyopathy and suspected myocarditis without confirmed cardiac tissue inflammation in histopathology assays were included and divided into groups: with preserved EF and reduced EF. After echocardiographic analysis of diastolic dysfunction we identified 2 preserved EF subgroups (normal diastolic function (NDF) and impaired relaxation (IR)) and 3 reduced EF subgroups (NDF, IR, and pseudonormalization). Patients with preserved EF and NDF formed the control group. Tissue desmin staining revealed 4 types of desmin expression: I - normal, with regular pattern of cross-section, IIA - increased with regular pattern, IIB - increased, with irregular pattern and presence of aggregates, III - decreased/lack desmin.. Desmin I was observed only in patients with NDF n=8 (100%) in preserved EF and reduced EF, desmin IIA in NDF n=8 (33%) in preserved EF and n=5 (33%) in reduced EF and IR n=16 (66%) in preserved EF and n=10 (66%) in reduced EF. Desmin IIB and III were observed in patients with reduced EF and diastolic dysfunction: IR and pseudonormalization n=9 (39%) and n=2 (29%); n=14 (61%) and n=5 (71%), respectively. Desmin was found to be an independent predictor of diastolic function parameters β=-0.63, R(2)=0.52 for E'; β=0.54, R(2)=0.42 for E/E'.. Increasing desmin abnormalities were correlated with diastolic dysfunction progression. Desmin expression represents a novel factor contributing or paralleling the development of diastolic dysfunction.

Topics: Adult; Cardiomyopathies; Desmin; Female; Humans; Male; Middle Aged; Myocarditis; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Remodeling

The soluble form of ST2 (sST2) is a novel laboratory parameter for cardiac risk prediction, and over the past years, several studies have tried to evaluate its utility, especially in the management of heart failure. We investigated whether increased serum levels of sST2 show a characteristic pathomorphologic pattern in 3-Tesla cardiac magnetic resonance imaging (CMRI).. One hundred and fifty-six patients referred to 3T CMRI due to suspected coronary artery disease (CAD) or myocarditis were prospectively enrolled in the study. Ninety patients were diagnosed with CAD, 22 patients with myocarditis, and 44 patients, who constituted the reference group, showed no pathologic CMRI pattern.. There was no significant difference between the sST2 values for patients in the reference group and patients with CAD or myocarditis. The sST2 concentration showed a weak correlation with the NYHA functional class (P = 0.002, r = 0.22), but correlation of sST2 and LGE, left ventricular parameters, and LVEF could not be seen. In contrast NT-proBNP was positively correlated to left ventricular parameters, LGE, and NYHA class function (P < 0.05). Additionally, it showed an inverse relationship to LVEF (P < 0.001, r = - 0.42).. Soluble ST2 is not able to detect myocardial scar and should not be used alone as a parameter for detection of inflammation and myocardial scar formation.

Topics: Adult; Aged; Biomarkers; Case-Control Studies; Cicatrix; Coronary Artery Disease; Female; Fibrosis; Humans; Interleukin-1 Receptor-Like 1 Protein; Magnetic Resonance Imaging; Male; Middle Aged; Myocarditis; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Receptors, Cell Surface; Stroke Volume; Up-Regulation; Ventricular Function, Left

To investigate the clinical features and prognostic factors in children with fulminant myocarditis.. The clinical data of 24 children with fulminant myocarditis were retrospectively analyzed. According to the prognosis, these children were classified into two groups: survival (n=12) and death (n=12). The risk factors influencing prognosis in children with fulminant myocarditis were identified by logistic regression analysis.. Among the 24 cases of fulminant myocarditis, gastrointestinal symptoms were found as initial symptoms in 14 cases, neurological symptoms in 12 cases, respiratory symptoms in 1 case, and cardiac symptoms in 2 cases. On admission, serum levels of creatine kinase MB, troponin I, and brain natriuretic peptide (BNP) were all increased. Besides, left ventricular ejection fraction (LVEF) decreased in 22 cases (92%), cardiothoracic ratio increased in 10 cases, third-degree atrioventricular block was observed in 8 cases, ST-segment changes were found in 11 cases and ventricular tachycardia was identified in 2 cases. LVEF in the death group was lower than in the survival group (P<0.05), while the peak level of serum BNP during hospitalization in the death group was higher than in the survival group (P<0.05). The multivariate logistic regression analysis revealed that LVEF was the risk factor influencing prognosis (OR=7.418; P<0.05).. Fulminant myocarditis has no specific clinical features in children. A decreased LVEF is a risk factor for poor prognosis in children with fulminant myocarditis.

Topics: Adolescent; Child; Creatine Kinase, MB Form; Electrocardiography; Female; Humans; Infant; Logistic Models; Male; Myocarditis; Natriuretic Peptide, Brain; Prognosis; Ventricular Function, Left

A previously healthy young man presented with a 12-hour history of sudden dyspnea and severe chest pain at rest. Initial findings of physical examination, electrocardiogram and chest radiography showed typical pericarditis and clinical instability. Echocardiogram revealed small pericardial effusion with right ventricle dilatation. The patient was admitted in the ICU; a new echocardiogram revealed moderate pericardial effusion and diagnosis of pericarditis complicated with acute cardiac tamponade was established. The patient transiently improved after pericardial window. In the following hours, the diagnosis of myocarditis with predominantly right ventricular involvement (MPRVI) with severe right heart failure was supported by clinical, chest radiography and echocardiogram data, despite normal B-type natriuretic peptide. On day 2, cardiac troponin I detection was observed. By day 3, B-type natriuretic peptide in the range of ventricular dysfunction was identified. Cardiovascular magnetic resonance findings supported the diagnosis of MPRVI. A systematic MEDLINE/PubMed from 1993 to 2013 does not identify any cases of MPRVI related to systemic lupus erythematosus. Simultaneous acute MPRVI with normal B-type natriuretic peptide and acute cardiac tamponade heralding the diagnosis of systemic lupus erythematosus, to the best of our knowledge, has not been previously described.

Topics: Adult; Cardiac Tamponade; Heart Ventricles; Humans; Lupus Erythematosus, Systemic; Male; Myocarditis; Natriuretic Peptide, Brain; Pericarditis

Myocarditis and dilated cardiomyopathy (DCM) are inflammatory diseases of the myocardium, for which appropriate treatment remains a major clinical challenge. Oleanolic acid (OA), a natural triterpene widely distributed in food and medicinal plants, possesses a large range of biological effects with beneficial properties for health and disease prevention. Several experimental approaches have shown its cardioprotective actions, and OA has recently been proven effective for treating Th1 cell-mediated inflammatory diseases; however, its effect on inflammatory heart disorders, including myocarditis, has not yet been addressed. Therefore, the present study was undertaken to determine the effectiveness of OA in prevention and treatment of experimental autoimmune myocarditis (EAM). The utility of OA was evaluated in vivo through their administration to cardiac α-myosin (MyHc-α614-629)-immunized BALB/c mice from day 0 or day 21 post-immunization to the end of the experiment, and in vitro through their addition to stimulated-cardiac cells. Prophylactic and therapeutic administration of OA dramatically decreased disease severity: the heart weight/body weight ratio as well as plasma levels of brain natriuretic peptide and myosin-specific autoantibodies production were significantly reduced in OA-treated EAM animals, compared with untreated ones. Histological heart analysis showed that OA-treatment diminished cell infiltration, fibrosis and dystrophic calcifications. OA also decreased proliferation of cardiac fibroblast in vitro and attenuated calcium and collagen deposition induced by relevant cytokines of active myocarditis. Furthermore, in OA-treated EAM mice the number of Treg cells and the production of IL-10 and IL-35 were markedly increased, while proinflammatory and profibrotic cytokines were significantly reduced. We demonstrate that OA ameliorates both developing and established EAM by promoting an antiinflammatory cytokine profile and by interfering with the generation of cardiac-specific autoantibodies, as well as through direct protective effects on cardiac cells. Therefore, we envision this natural product as novel helpful tool for intervention in inflammatory cardiomyopathies including myocarditis.

Topics: Animals; Autoantibodies; Autoimmune Diseases; Body Weight; Calcium; Cardiomyopathy, Dilated; Cardiotonic Agents; Cell Proliferation; Female; Fibroblasts; Humans; Immunomodulation; Interleukin-10; Interleukins; Male; Mice; Mice, Inbred BALB C; Myocarditis; Myocardium; Myosin Heavy Chains; Natriuretic Peptide, Brain; Oleanolic Acid; Organ Size; Peptides; T-Lymphocytes, Regulatory

Myocarditis might be associated with increased markers of myocardial injury. However, data on novel biomarkers, such as high-sensitive Troponin T (hs-TnT) or Copeptin, are lacking. This study aimed to determine the diagnostic and prognostic utility of biomarkers in patients with suspected myocarditis.. Seventy patients with clinically suspected myocarditis (age 43.4 ± 14 years, 76 % male, ejection fraction 36.9 ± 17.8) underwent endomyocardial biopsy (EMB) and were followed for 7.5 (2-21) months. At the time of EMB, blood samples to evaluate concentrations of hs-TnT, Copeptin, NT-proBNP and mid-regional pro-adrenomedullin (MR-proADM) were collected.. According to EMB, 6 patients were diagnosed with acute myocarditis (AM) and 36 patients with chronic myocarditis (CM). In 28 patients, EMB revealed no myocardial inflammation (NM). Acute myocarditis was associated with the highest concentrations of hs-TnT compared to other groups (AM 262.9 pg/ml (61.4-884.2); CM 20.4 pg/ml (15.6-20.4); NM 19.5 pg/ml (13.8-50.7); p < 0.0001). No significant differences existed in the Copeptin, NT-proBNP, and MR-proADM concentrations between the groups. The concentration of hs-TnT was significantly higher in myocarditis when myocardial viral genome was detected (37.4 pg/ml (21.9-163.6) vs. 20 pg/ml (14-44.4); p = 0.042). During follow-up, only NT-proBNP in the highest quartile (>4,225 ng/ml) was predictive for cardiac death or heart transplantation (hazard ratio 9.2; 95% confidence interval 1.7-50; p = 0.011).. Biopsy-proven acute and viral myocarditis is associated with elevated concentrations of hs-TnT. Elevated hs-TnT is highly suggestive of acute myocarditis, if other causes of increased myocardial necrosis markers such as myocardial infarction have been systematically excluded.

Topics: Acute Disease; Adult; Aged; Biomarkers; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocarditis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Troponin T; Young Adult

 Dengue is a disease whose clinical manifestations range from asymptomatic infections to a severe disease. There have been some previous reports of myocardial involvement in dengue, but this association has not been completely established..  From January to July of 2011, patients hospitalized with dengue, confirmed through dengue nonstructural protein 1 and/or immunoglobulin M detection, were included in this study and troponin I and N terminal fragment of B-type natriuretic peptide levels were determined. Patients with abnormal biomarkers underwent echocardiography and when any abnormality was detected, they underwent cardiac magnetic resonance imaging..  Eighty-one patients were evaluated and 12 patients (15%) presented with elevated biomarker levels. Compared to controls, they had higher leukocyte (P < .001) and platelet counts (P = .005); higher C-reactive protein (P = .02), and a lower viral load (P = .03). There was no difference according to clinical dengue classification; dengue hemorrhagic fever/dengue shock syndrome severity; duration of symptoms; or prevalence of secondary infection between the 2 groups. Two patients died secondary to cardiogenic shock before imaging studies. Necroscopic findings were compatible to myocarditis in both, and immunohistochemistry for dengue virus showed increased staining on mononuclear cells located in the myocardial tissue. Of the 10 patients who underwent echocardiography, depressed left ventricular ejection fraction (LVEF) was identified in 1, left ventricular segmental abnormalities with preserved LVEF in 2, and an important pericardial effusion with tamponade in another. Cardiac involvement was confirmed by CMR in these 4 patients..  Dengue viruses were shown to cause cardiac disease with clinical manifestations ranging from mild elevation of biomarkers to myocarditis and/or pericarditis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Child; Child, Preschool; Dengue; Dengue Virus; Female; Humans; Infant; Male; Middle Aged; Myocarditis; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Shock, Cardiogenic; Troponin I; Viral Load

Endomycocardial biopsies have demonstrated that subclinical myocarditis is a universal feature of acute Kawasaki disease (KD).. We investigated biochemical evidence of myocardial strain, oxidative stress, and cardiomyocyte injury in 55 acute KD subjects (30 with paired convalescent samples), 54 febrile control (FC), and 50 healthy control (HC) children by measuring concentrations of cardiovascular biomarkers.. Levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and soluble ST2 (sST2) were elevated in acute vs. convalescent KD, FC, and HC (p≤0.002), while γ-glutamyl transferase and alanine amino transferase as measures of oxidative stress were increased in acute vs. FC (p≤0.0002). Cardiac troponin I (cTnI) levels, using a highly sensitive assay, were elevated in 30% and 40% of paired acute and convalescent KD subjects, respectively, and normalized within two years of disease onset. NT-proBNP and sST2 negatively correlated with deceleration time, but only NT-proBNP correlated with MV E:A ratio and internal diameter of the coronary arteries (RCA/LAD Zworst).. NT-proBNP and sST2 were elevated in acute KD subjects and correlated with impaired myocardial relaxation. These findings, combined with elevated levels of cTnI, suggest that both cardiomyocyte stress and cell death are associated with myocardial inflammation in acute KD.

Topics: Acute Disease; Adolescent; Biomarkers; Child; Child, Preschool; Female; Humans; Infant; Male; Mucocutaneous Lymph Node Syndrome; Myocarditis; Natriuretic Peptide, Brain; Peptide Fragments; Troponin I

The association between HCV infection and myocardial disorders remains unclear. This study aimed to assess whether or not HCV infection influences myocardial dysfunction by the use of NT-proBNP, a sensitive marker of myocardial dysfunction. A total of 198 participants [99 patients with chronic HCV infection (aged 46-68 years) and 99 anti-HCV-negative sex and age matched controls] were examined. Serum HCV-RNA level and HCV genotype were tested and liver biopsy was done only for the patient group. The NT-proBNP concentration of the HCV patients (mean 71.6 ± 79.1 pg/ml; median 46.0 pg/ml, range 5.0-400.0) was significantly higher than that of the controls (mean 39.8 ± 24.4 pg/ml; median 35.8 pg/ml, range 7.0-108.0) (P < 0.05). 20.0 % of the HCV patients and 0.6 % of the controls had high NT-proBNP (higher than 125 pg/ml; the single cut off point for patients under 75 years of age) (P < 0.05). Stepwise multiple regression analysis revealed that chronic HCV infection was independently correlated with NT-proBNP level after adjustment for parameters that might influence NT-proBNP (P = 0.005). Our data suggest that chronic HCV infection is associated with increased NT-proBNP, indicating that chronic HCV infection might induce myocardial dysfunction.

Topics: Aged; Biomarkers; Biopsy; Cross-Sectional Studies; Female; Heart Ventricles; Hepacivirus; Hepatitis C Antibodies; Hepatitis C, Chronic; Humans; Japan; Liver; Male; Middle Aged; Molecular Typing; Myocarditis; Natriuretic Peptide, Brain; Peptide Fragments; RNA, Viral; Up-Regulation; Ventricular Dysfunction

Injury to the heart can result in cardiomyocyte hypertrophy, fibrosis, and cell death. Myocarditis sometimes progresses to dilated cardiomyopathy. We previously reported that ONO-1301, a synthetic prostacyclin agonist with thromboxane-synthase inhibitory activity, promotes production of hepatocyte growth factor (HGF) from various cell types and ameliorates ischemia-induced left ventricle dysfunction in the mouse, rat and pig. Here, we investigated the therapeutic efficacy of ONO-1301 in a rat model of myosin-induced experimental autoimmune myocarditis, in which the heart transits from an acute inflammatory phase to a chronic dilated cardiomyopathy phase. Four weeks after myosin injection to Lewis rats, ONO-1301 (6 mg/kg/day) was orally administered for 4 weeks (ONO-1301 group). Hemodynamic parameters and plasma brain natriuretic peptide (BNP) level were significantly improved by ONO-1301. Histological analysis revealed that capillary density in the myocardium was significantly increased by ONO-1301. ONO-1301 increased circulating endothelial progenitor cells (EPC) as determined by FACS analysis. These beneficial effects of ONO-1301 were partially abrogated by a neutralizing anti-HGF antibody (8 mg/kg/dose). These findings indicate beneficial effects of ONO-1301 in a rat experimental autoimmune myocarditis model.

Topics: Administration, Oral; Animals; Autoimmune Diseases; Cardiomyopathy, Dilated; Disease Models, Animal; Endothelial Cells; Hemodynamics; Male; Myocarditis; Myosins; Natriuretic Peptide, Brain; Pyridines; Rats; Rats, Inbred Lew; Stem Cells

This study aimed to evaluate the performance of cardiac magnetic resonance (CMR), cardiac biomarkers, and endomyocardial biopsy (EMB) results to predict left ventricular reverse remodeling (LVRR) in individuals with recent-onset dilated cardiomyopathy (DCM).. LVRR is a marker of a favorable prognosis in individuals with recent-onset DCM. We used the aforementioned novel methods of prognostication to predict this event.. A total of 44 consecutive patients with recent-onset DCM underwent at baseline CMR, measurement of biomarkers and EMB together with conventional methods, including cardiopulmonary exercise testing and echocardiography. Measurement of B-type natriuretic peptide (BNP) and the cardiological examination were repeated at 3, 6, and 12 months. CMR was repeated at 12 months. LVRR was defined as an absolute increase in left ventricular ejection fraction from ≥10% to a final value of >35% accompanied by a decrease in left ventricular end-diastolic dimension ≥10% at 12 months of follow-up.. LVRR was observed in 20 individuals (45%) at 12 months. At baseline, a lower extent of late gadolinium enhancement (odds ratio [OR]: 0.67 [95% confidence interval (CI): 0.50 to 0.90]; p = 0.008) and a higher myocardial edema ratio (OR: 1.45 [95% CI: 1.04 to 2.02]; p = 0.027) measured by CMR were independent predictors of LVRR. At 3 months, the latest BNP plasma level (OR: 0.14 [95% CI: 0.02 to 0.94] per log BNP; p = 0.047) was the strongest predictor of LVRR.. Both CMR and serial BNP testing provide a better prediction of LVRR in recent-onset DCM than EMB results, other biomarkers, and the conventional methods of follow-up.

Topics: Adult; Biomarkers; Biopsy; Cardiomyopathy, Dilated; Contrast Media; Diastole; Echocardiography; Edema; Endocardium; Exercise Test; Female; Follow-Up Studies; Humans; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Multivariate Analysis; Myocarditis; Myocardium; Natriuretic Peptide, Brain; Organometallic Compounds; Sensitivity and Specificity; Stroke Volume; Ventricular Remodeling

To explore the brain natriuretic peptide (BNP) on prognostic value in patients with viral myocarditis.. A total of 48 patients with viral myocarditis and 42 healthy people were enrolled and followed up for two years. The NYHA class and LVEF were recorded and the concentration of BNP were measured.. The concentration of BNP were higher and EF were lower in patients with viral myocarditis (P < 0.01) than contrast people. Higher levels of plasma BNP were related to higher mortality.. Levels of brain natriuretic peptide measured in the plasma could be a useful biochemical marker for the myocarditis, and high concentration of BNP may correlate with poor prognosis in patients with myocarditis.

Topics: Adolescent; Adult; Biomarkers; Child; Female; Humans; Male; Middle Aged; Myocarditis; Natriuretic Peptide, Brain; Prognosis; Ventricular Function, Left; Virus Diseases

Homing of cardiac myosin-specific CD4-positive T cells into the myocardium is the initial pathologic event of experimental autoimmune myocarditis (EAM). Subsequently, various bystander inflammatory cells are recruited into the myocardium crossing vascular endothelial cell walls. Sulfated polysaccharide fucoidan binds selectin nonselectively and blocks its function. Therefore, this study was designed to evaluate whether in vivo fucoidan treatment can improve EAM. A 21-day infusion of physiological saline or fucoidan was administrated intraperitoneally to the rats with sham operation (sham-saline, n = 5; sham-fucoidan, n = 6) or those with cardiac myosin injection (EAM-saline, n = 10; EAM-fucoidan, n = 10). After 3 weeks, fucoidan treatment improved left ventricular ejection fraction (79.04 ± 2.81 vs 65.94% ± 3.22%; P < .01 vs EAM-saline) with a reduced ratio of heart weight to body weight (4.016 ± 0.239 vs 4.975 ± 0.252 mg/g; P < .05 vs EAM-saline) in EAM. Furthermore, fucoidan treatment decreased serum levels of BNP (292.0 ± 53.4 vs 507.4 ± 89.2 ng/mL; P < .05 vs EAM-saline) and the myocarditis area (31.66 ± 1.53 vs 42.51% ± 3.24%; P < .01 vs EAM-saline) in EAM. These beneficial effects of fucoidan were accompanied by inhibition of both macrophage and CD4-positive T-cell infiltration into the myocardium. Fucoidan, a nonselective selectin blocker, attenuates the progression of EAM. This observation may be explained, at least in part, by blocking the extravasation of inflammatory cells into the myocardium.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Autoimmune Diseases; CD4 Antigens; Cytokines; Heart; Macrophages; Male; Myocarditis; Myocardium; Natriuretic Peptide, Brain; Organ Size; P-Selectin; Polysaccharides; Random Allocation; Rats; Rats, Inbred Lew; Stroke Volume; T-Lymphocytes

Kawasaki disease, a systemic vasculitis of unknown etiology, develops frequently in infants and demonstrates a variety of clinical symptoms during the disease course. The most important complication, coronary artery lesions, is found in 15-25% of untreated patients. Meanwhile, acute myocarditis, another complication that can occur during the acute phase of severe systemic vasculitis, has been found in more than 50% of affected individuals when asymptomatic cases are included. However, cases that require treatment are rare as reported by Yoshikawa et al. (Circ J 70:202-205, 2006). As for neural complications, aseptic meningitis is well known, but it is extremely rare for these patients to develop encephalitis or encephalopathy as reported by Imai et al. (Jpn Soc Emerg Pediatr 8:50-55, 2009). Recently reported magnetic resonance images (MRIs) have shown reversible lesions in the median splenium of patients complicated with encephalitis or encephalopathy. Reversible lesions have also been observed after the administration of an antiepileptic agent, drastic weight loss, and development of metabolic abnormalities as reported by Massimo et al. (Neuroradiology 49:541-544, 2007) and Tada et al. (Neurology 63:1854-1858, 2004). Aggressive therapy for such lesions is not considered necessary because most disappear without neurologic aftereffects. However, the clinical significance and pathogenesis of the condition remain largely unknown. We present the first known report of a Kawasaki disease case complicated with acute myocarditis and mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). These findings may be valuable for the diagnosis and treatment of affected patients.

Topics: Acute Disease; Adolescent; C-Reactive Protein; Coronary Aneurysm; Corpus Callosum; Diffusion Magnetic Resonance Imaging; Echocardiography; Encephalitis; Female; Follow-Up Studies; gamma-Globulins; Humans; Mucocutaneous Lymph Node Syndrome; Myocarditis; Natriuretic Peptide, Brain; Peptide Fragments; Tomography, X-Ray Computed

During the past 3 years, seven potential candidates for mechanical circulatory support (MCS) were treated at our center. Ultimately, only one of them needed MCS (extracorporeal membrane oxygenation [ECMO] for 16 days), although 5 years earlier, all would have been considered for MCS at our center. Seven consecutive patients were seen in this period: four toddlers (three suffering from fulminant myocarditis and one with dilated cardiomyopathy associated with spongy myocardium) and three adolescents (two with postmyocarditis cardiomyopathy and one with hypertrophic cardiomyopathy and severe restrictive dysfunction after an ischemic event with cardiopulmonary resuscitation [stunned heart]). All patients presented in acute cardiocirculatory decompensation. All were admitted to the intensive care unit (ICU); all but one were sedated and intubated. A combination of levosimendan, milrinone, and nesiritide was administered to all patients. Use of catecholamines was kept short (<48 h in six individuals). MCS (ECMO, Berlin Heart Excor Pediatric, and Heartware) was always available. MCS initiation was indicated in only one patient, who was developing progressive multiorgan failure (MOF). The three toddlers with myocarditis recovered with complete normalization of myocardial function within 6 months. The fourth toddler is still at the ICU while waiting for transplantation. The three adolescents were listed with high urgency for heart transplantation, and all received a graft within 3 weeks. The adolescent with the stunned heart developed progressive MOF and was successfully supported with ECMO until transplantation. All six patients with completed course were discharged home in New York Heart Association Heart Failure Functional Classification System I condition without neurological deficits. Combined use of levosimendan, milrinone, and nesiritide, avoidance of catecholamines as much as possible, and MCS as backup are the new strategies at our center. This cardioprotective approach gives excellent outcome at lower risk and better cost-effectiveness in our pediatric patients with acute heart failure. Pediatric trials are recommended to evaluate combined use of newer cardioprotective drugs.

Topics: Adolescent; Cardiomyopathies; Cardiotonic Agents; Catecholamines; Child, Preschool; Extracorporeal Membrane Oxygenation; Female; Heart Failure; Humans; Hydrazones; Infant; Male; Milrinone; Myocarditis; Natriuretic Agents; Natriuretic Peptide, Brain; Pyridazines; Simendan

Lipocalin-2/neutrophil gelatinase-B associated lipocalin (Lcn2/NGAL) is involved in the transport of iron and seems to play an important role in inflammation. A recent study has reported that it is also expressed in the failing heart and may be a biomarker not only for renal failure but also for heart failure. Because Lcn2/NGAL is thought to be induced by interleukin-1, it might be strongly induced in the presence of myocarditis.. This study investigated the expression of Lcn2/NGAL in rat experimental autoimmune myocarditis (EAM) and in human myocarditis. In EAM hearts, the expression of Lcn2/NGAL was markedly increased (>100-fold at an early stage), and in human myocarditis it was also highly expressed compared with non-inflammatory failing hearts. Lcn2/NGAL expressing cells in hearts with EAM and human myocarditis were identified as cardiomyocytes, vascular wall cells, fibroblasts and neutrophils. Lcn2/NGAL in EAM rats was also expressed in the liver. Plasma Lcn2/NGAL levels abruptly increased at an early stage of EAM, and high levels were initially sustained during the inflammatory stage, then decreased with recovery. In contrast, levels of B-type natriuretic peptide increased only slowly as the disease progressed.. Cardiomyocytes, vascular wall cells and fibroblasts in myocarditis strongly express Lcn2/NGAL via proinflammatory cytokines.

Topics: Acute-Phase Proteins; Aged; Animals; Autoimmune Diseases; Disease Models, Animal; Female; Fibroblasts; Gene Expression; Heart Failure; Humans; Immunization; Interleukin-1beta; Lipocalin-2; Lipocalins; Male; Matrix Metalloproteinase 9; Middle Aged; Myocarditis; Myocytes, Cardiac; Myosins; Natriuretic Peptide, Brain; Proto-Oncogene Proteins; Rats; Swine; Young Adult

Acute rheumatic carditis is still an important cause of cardiac failure in developing countries. B-type natriuretic peptides, especially N-terminal segment of its prohormone are now recognised as essential parts of cardiologic evaluation. Increased plasma concentrations of B-type natriuretic peptide and its prohormone are markers of cardiac failure and hypoxia in adults.. To measure the prohormone levels in children with acute rheumatic carditis and to determine whether its concentrations correlate with clinical and laboratory findings.. A total of 24 children with acute rheumatic carditis and 23 age and sex-matched healthy subjects were entered in the study. Transthoracic echocardiography was performed in all patients to assess the severity of the valve insufficiency and cardiac dysfunction. The prohormone plasma levels were tested for correlation with cardiac dysfunction and other biochemical markers, such as C-reactive protein, erythrocyte sedimentation rate, and anti-streptolysin-O titter.. The prohormone plasma concentrations were significantly higher in children with acute rheumatic carditis than in control subjects at the time of diagnosis. A significant decrease of the plasma level was detected among patients after treatments (6-8 weeks).. We found increased plasma prohormone levels in children with acute rheumatic carditis in the acute stage of illness compared with healthy subjects. Another result is increased plasma prohormone levels as acute rheumatic carditis are reversible.

Topics: Acute Disease; Adolescent; Biomarkers; Child; Disease Progression; Female; Follow-Up Studies; Heart Failure; Humans; Hypoxia; Immunoassay; Male; Myocarditis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Retrospective Studies; Rheumatic Heart Disease

Whereas C-reactive protein (CRP) is acknowledged as a cardiovascular risk marker, there is ongoing discussion about its role as a risk factor. Previous studies focused on the effects of CRP on ischaemic heart failure and atherosclerosis. In this study we investigated distribution of CRP, the Terminal Complement Complex (C5b-9) and macrophages (CD68) in the myocardium of patients suffering from non-ischaemic heart failure and their implication on clinical parameters. Endomyocardial biopsies were taken from 66 patients suffering from dilated cardiomyopathy (DCM). Biopsies were analysed by immunohistochemical and immunofluorescent staining for CRP, C5b-9 and CD68. Viral DNA/RNA for adenovirus, enterovirus, parvovirus B19 and human herpes virus 6 was detected by PCR and Southern blot analysis. Myocardial biopsy findings were correlated with plasma level of hsCRP and NT-proBNP as well as echocardiography, exercise test and NYHA class. In 18 (27%) patients, a positive staining for CRP and in 57 (86%) patients a positive staining for C5b-9 was detected. All patients showed myocardial infiltration with macrophages with an average of 39 cells/mm(2). CRP, C5b-9 and CD68 co-localised within the myocardium. No correlation was observed for inflammatory proteins and plasma level of hsCRP, NT-proBNP and clinical parameters. CRP is frequently present in the myocardium of patients suffering from DCM and co-localises with C5b-9 and macrophages. CRP may contribute to myocardial damage in DCM via activation of the complement system and chemotaxis of macrophages.

Topics: Adenoviridae; Adult; Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biopsy; C-Reactive Protein; Cardiomyopathy, Dilated; Complement Membrane Attack Complex; DNA, Viral; Enterovirus; Exercise Test; Female; Heart Failure; Herpesvirus 6, Human; Humans; Macrophages; Male; Middle Aged; Myocarditis; Myocardium; Natriuretic Peptide, Brain; Parvovirus B19, Human; Peptide Fragments; RNA, Viral; Ultrasonography

Idiopathic dilated cardiomyopathy (IDC) is characterized by sympathetic nervous overactivity, inflammation and neurohumoral activation; however, their interrelationships are poorly understood.. We studied 99 patients with IDC (age 54 +/- 1 years, left ventricular ejection fraction (EF) 40 +/- 1%, maximum oxygen uptake (VO(2)max) 20 +/- 1 ml kg(-1) min(-2), mean +/- SEM) by using (123)I-metaiodobenzylguanidine (MIBG) imaging. MIBG washout and MIBG heart/mediastinum (H/M)-ratio at 4 h postinjection were calculated. In addition, the plasma levels of interleukin (IL)-6 and N-terminal B-type natriuretic peptide (NT-proBNP) were measured. MIBG washout and MIBG H/M ratio had a significant correlation with IL-6 (r = 0.42, P<0.001 and r = -0.31, P<0.01) and NT-proBNP (r = 0.48, P<0.001 and r = -0.40, P<0.001). During a median follow-up of 4.1 years, 20 patients (20%) had an adverse cardiac event (death, heart transplantation or application of biventricular pacemaker or implantable cardioverter-defibrillator). In these patients, MIBG washout was higher (53 +/- 4 versus 40 +/- 2%, P = 0.01) and H/M ratio lower (1.38 +/- 0.04 versus 1.51 +/- 0.02, P = 0.01) than in patients without an event.. In dilated cardiomyopathy, myocardial sympathetic innervation and activity are related to inflammation and neurohumoral activation. These relationships are at least partly independent of left ventricular function and exercise capacity.

Topics: Cardiomyopathy, Dilated; Female; Humans; Interleukin-6; Male; Middle Aged; Myocarditis; Natriuretic Peptide, Brain; Neurotransmitter Agents; Peptide Fragments; Sympathetic Nervous System; Ventricular Dysfunction, Left

Fulminant myocarditis with rapid onset of symptoms and hemodynamic compromise is a rare indication for mechanical support. Because of the potentially reversible nature of this illness, advanced mechanical circulatory support is warranted to achieve recovery or as a bridge to transplantation. Circulatory device options currently available allow for a phased implementation of support modalities in a manner that reduces costs and patient risk. We present a patient with fulminant myocarditis where extracorporeal membrane oxygenation (ECMO) support escalated to short-term Levitronix CentriMag (Levitronix, Waltham, MA) biventricular assist devices (BiVADs). These in turn were exchanged, without major surgery, to long-term paracorporeal VADs (Thoratec, Pleasanton, CA). After rehabilitation and nearly total recovery, the patient was weaned from mechanical circulatory support after 104 cumulative days.

Topics: Adult; Anticoagulants; Atrial Natriuretic Factor; Blood Coagulation; Cardiopulmonary Resuscitation; Echocardiography; Extracorporeal Membrane Oxygenation; Female; Heart Arrest; Heart-Assist Devices; Heparin; Humans; Myocarditis; Natriuretic Peptide, Brain; Shock, Cardiogenic; Stroke Volume; Treatment Outcome

The cardiac natriuretic peptides atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) are discoordinately regulated in myocardial inflammation associated with acute allograft rejection in humans and during in vitro exposure of cardiocyte cultures to some proinflammatory cytokines. We used experimental autoimmune myocarditis (EAM) to determine whether the discoordinate regulation of ANF and BNP was specific to the situations above or was generally associated with other types of myocardial inflammation. The dependency of this process to angiotensin signaling was also determined, given that previous work demonstrated beneficial effects of the angiotensin receptor blocker olmesartan in myocarditis. Histopathological changes, plasma and cardiac ANF, BNP, and selected cytokines gene expression as well as plasma cytokine levels using a cytokine array were determined in EAM, angiotensin receptor blocker-treated, and control rats. It was found that EAM specifically increases BNP but not ANF circulating levels, thus mimicking the findings in acute cardiac allograft rejection and the effect of some proinflammatory cytokines on cardiocyte cultures in vitro. Plasma cytokine array and real-time PCR revealed that lipopolysaccharide-induced CXC chemokine, monocyte chemotactic protein-1, and tissue inhibitor of metalloproteinase-1 were increased in plasma and in the myocardium of EAM rats. Olmesartan treatment reversed virtually all neuroendocrine and histopathological cardiac changes induced by EAM, thus providing a mechanistic insight into this phenomenon. It is concluded that the inflammatory process contributes specific cytokines, leading to the disregulation of cardiac ANF and BNP production observed during myocardial inflammation, and that this process is angiotensin receptor 1 dependent.

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Atrial Natriuretic Factor; Blood Pressure; Cytokines; Disease Models, Animal; Imidazoles; Mycobacterium tuberculosis; Myocarditis; Myocardium; Natriuretic Peptide, Brain; Polymerase Chain Reaction; Protein Array Analysis; Rats; Rats, Inbred Lew; Receptor, Angiotensin, Type 1; RNA, Messenger; Tetrazoles; Up-Regulation

The aim of study is to determine the prevalence of hepatitis C virus (HCV) infection and myocardial injury among patients enrolled in the Myocarditis Treatment Trial. HCV infection has recently been noted in patients with cardiomyopathies and myocarditis. However, prevalence of HCV infection in myocarditis and heart failure remains to be clarified.. Patients with heart failure up to 2 years in duration without a distinct cause were enrolled in the trial between 1986 and 1990. Frozen blood samples were available from 1355 among 2233 patients enrolled and examined for presence of anti-HCV antibodies, circulating cardiac troponins I and T, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Anti-HCV antibodies were identified in 59 of 1355 patients (4.4%). This higher prevalence of HCV infection than that observed in the general US population (1.8%), varied widely (0-15%) among the different medical centers and regions. The concentrations of circulating cardiac troponin (cTn) I were elevated in 17 of 56 patients (30%), and cTnT was detectable in 28 of 59 patients (48%) with HCV antibodies, suggesting the persistence of ongoing myocardial injury. The concentrations of NT-proBNP were elevated in 42 of 42 patients (100%) with HCV antibodies, (10,000 +/- 5860 pg/mL), a mean value significantly greater than in 1276 patients without HCV antibody (2508 +/- 160 pg/mL, P < .0001).. Anti-HCV antibodies were identifiable in sera stored for 13 to 17 years and were more prevalent in patients with myocarditis and HF than in the general population. In regions where its prevalence is high, HCV infection may be an important cause of myocarditis and HF. NT-proBNP is a more sensitive marker of myocardial injury than cardiac troponins in patients with heart failure from HCV myocarditis.

Topics: Biomarkers; Cardiomyopathy, Dilated; Comorbidity; Heart; Heart Failure; Hepatitis C; Humans; Myocarditis; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; RNA, Viral; Troponin I; Troponin T; United States

B-type natriuretic peptide (BNP) is chronically elevated in heart transplantation and reflects diastolic dysfunction, cardiac allograft vasculopathy, and poor late outcome. This investigation studied peripheral gene expression signatures of elevated BNP concentrations in clinically quiescent heart transplant recipients in an effort to elucidate molecular correlates beyond hemodynamic perturbations.. We performed gene microarray analysis in peripheral blood mononuclear cells of 28 heart transplant recipients with clinical quiescence (absence of dyspnea or fatigue; normal left ventricular ejection fraction [EF >55%]; ISHLT biopsy score 0 or 1A; and normal hemodynamics [RAP <7 mm Hg, PCWP < or = 15 mm Hg, and CI > or = 2.5 L/min per m2]). BNP levels were performed using the Triage B-type Natriuretic Peptide test (Biosite Diagnostics Inc, San Diego, Calif) and median BNP concentration was 165 pg/mL. Seventy-eight probes (of 7370) mapped to 54 unique genes were significantly correlated with BNP concentrations (P<0.001). Of these, the strongest correlated genes (P<0.0001) were in the domains of gelsolin (actin cytoskeleton), matrix metallopeptidases (collagen degradation), platelet function, and immune activity (human leukocyte antigen system, heat shock protein, mast cell, and B-cell lineage).. In the clinically quiescent heart transplant recipient, an elevated BNP concentration is associated with molecular patterns that point to ongoing active cardiac structural remodeling, vascular injury, inflammation, and alloimmune processes. Thus, these findings allude to the notion that BNP elevation is not merely a hemodynamic marker but should be considered reflective of integrated processes that determine the balance between active cardiac allograft injury and repair.

Topics: Aged; Biomarkers; Biopsy; Cohort Studies; Endocardium; Female; Gene Expression Profiling; Graft Rejection; Heart Transplantation; Hemodynamics; Humans; Male; Middle Aged; Myocarditis; Natriuretic Peptide, Brain; Oligonucleotide Array Sequence Analysis; Postoperative Complications; Ventricular Remodeling

Hepatitis C virus (HCV) has been reported to be associated with cardiomyopathy. However, the mechanism of cardiomyopathy in chronic HCV infection is still unclear. Therefore, we investigate the development of cardiomyopathy in mice transgenic for the HCV-core gene. After the age of 12 months, mice developed cardiomyopathy that appeared as left ventricular dilatation, and systolic and diastolic dysfunction assessed by Doppler echocardiography. Histologically, hypertrophy of cardiomyocytes, cardiac fibrosis, disarray and scarcity of myofibrils, vacuolization and deformity of nuclei, myofibrillar lysis, streaming of Z-bands, and an increased number of bizarre-shaped mitochondria were found in HCV-core transgenic mice. These histological changes are just consistent with cardiomyopathy. In conclusion, the HCV-core protein directly plays an important role in the development of cardiomyopathy.

Topics: Actin Cytoskeleton; Animals; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Echocardiography, Doppler; Fibrosis; Gene Expression Regulation, Viral; Hepacivirus; Hepatitis C; Hypertrophy, Left Ventricular; Male; Mice; Mice, Transgenic; Mitochondria, Heart; Myocarditis; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; NF-kappa B; Organ Size; RNA, Messenger; RNA, Viral; Transcription Factor AP-1; Ventricular Dysfunction, Left; Viral Core Proteins

Topics: Animals; Antiviral Agents; Atrial Natriuretic Factor; Cardiomyopathies; Gene Expression Regulation, Viral; Heart; Heart Failure; Hepacivirus; Hepatitis C; Hepatitis C Antibodies; HLA-D Antigens; Humans; Interferons; Mice; Mice, Transgenic; Myocarditis; Myocardium; Natriuretic Peptide, Brain; NF-kappa B; Paraffin Embedding; Phenotype; Prevalence; RNA, Viral; Species Specificity; Transcription Factor AP-1; Viral Core Proteins

Myosin-induced autoimmune myocarditis in rats is a model of human dilated cardiomyopathy. Rapamycin is a potent immunosuppressant and specifically inactivates the mammalian target of rapamycin (mTOR). To examine the role of mTOR in autoimmune myocarditis, we administered rapamycin to rats immunized with cardiac myosin. Phosphorylation of p70 ribosomal S6 kinase 1 (S6K1), a target of mTOR, was increased by 6.9 fold in the heart tissue of myosin immunized rats. Rapamycin (2 mg/kg/day) completely suppressed S6K1 and S6 phosphorylation. The amount of interleukin-1beta, interferon-gamma, interleukin-2, or tumor necrosis factor-alpha mRNA in the heart tissue was markedly increased in myosin-immunized rats, and rapamycin significantly attenuated the cytokine gene expressions. Rapamycin improved the survival of the rats and preserved cardiac function. The plasma level of brain natriuretic peptide increased by 4.7 fold in myosin-immunized rats, and rapamycin attenuated the increase in plasma brain natriuretic peptide. The heart weight/tibial length ratio of vehicle-treated myosin-immunized rats was increased by 1.81 +/- 0.06 fold compared with vehicle-treated unimmunized rats, and rapamycin suppressed the increase in heart weight. Rapamycin decreased the cellular infiltration and fibrosis of the myocardium. The amount of phosphorylated S6 was increased in the infiltrating mononuclear cells in vehicle-treated myosin-immunized rats. Rapamycin significantly ameliorated myocardial injury and preserved cardiac function in a rat model of autoimmune myocarditis.

Topics: Animals; Autoimmunity; Cardiomyopathy, Dilated; Disease Models, Animal; Female; Gene Expression Regulation; Immunosuppressive Agents; Interferon-gamma; Interleukin-1; Interleukin-2; Myocarditis; Myosins; Natriuretic Peptide, Brain; Rats; Rats, Inbred Lew; Sirolimus; Treatment Outcome; Tumor Necrosis Factor-alpha

We assessed the significance of serum cytokine levels in patients with fulminant myocarditis.. Although many investigations have demonstrated the crucial role of cytokines in the development of myocarditis, it remains uncertain whether serum levels of cytokines enable one to predict the prognosis of human myocarditis, especially concerning cardiogenic shock (CS) requiring a mechanical cardiopulmonary support system (MCSS).. We studied 22 consecutive patients with fulminant myocarditis and compared them with 15 patients with acute myocardial infarction (AMI) requiring MCSS. The patients with myocarditis were classified into three groups: eight patients with CS requiring MCSS on admission (group 1); six patients who unexpectedly lapsed into CS requiring MCSS more than two days after catecholamine had been initiated (group 2); and eight patients without MCSS (group 3). Furthermore, 14 patients with myocarditis requiring MCSS were divided into a fatal group (n = 5) and a survival group (n = 9). Biochemical markers, including serum cytokine levels and hemodynamic variables on admission, were analyzed.. Serum levels of interleukin (IL)-10 and tumor necrosis factor-alpha, but not other cytokines, were significantly higher in myocarditis than in AMI. Only serum levels of IL-10 were significantly higher in group 1 and 2 than in group 3 (49.1 +/- 37.5/20.7 +/- 17.6 pg/ml vs. 2.4 +/- 1.1 pg/ml; p = 0.0008/0.0012). Serum IL-10 levels were also significantly higher in the fatal group than in the survival group with myocarditis (74.0 +/- 27.0 pg/ml vs. 16.4 +/- 8.8 pg/ml; p = 0.003).. Serum IL-10 levels on admission enabled one to predict subsequent CS requiring MCSS and mortality of fulminant myocarditis patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Female; Humans; Interferon-gamma; Interleukin-10; Japan; Male; Middle Aged; Myocardial Infarction; Myocarditis; Natriuretic Peptide, Brain; Patient Admission; Predictive Value of Tests; Prognosis; Severity of Illness Index; Survival Analysis; Treatment Outcome; Troponin T; Tumor Necrosis Factor-alpha

Topics: Biomarkers; Cytokines; Humans; Interferon-gamma; Interleukin-10; Myocardial Infarction; Myocarditis; Natriuretic Peptide, Brain; Patient Admission; Troponin T; Tumor Necrosis Factor-alpha

Topics: Biomarkers; Coronary Artery Disease; Humans; Interleukin-6; Myocarditis; Myocardium; Natriuretic Peptide, Brain; Necrosis; Nerve Tissue Proteins; Peptide Fragments; Troponin T

Diagnosis of perimyocarditis is often very challenging. Clinical presentation includes chest pain and ECG changes which are difficult to interpret. Clinical course is usually mild, however, some patients develop heart failure symptoms and require aggressive treatment. Plasma b-type natriuretic peptide (BNP) is a marker of the hemodynamical impairment of the heart. Its diagnostic role in patients with acute perimyocarditis has not yet been examined.. To assess the usefulness of BNP measurement in the diagnosis of perimyocarditis.. The study group consisted of 14 consecutive patients (13 males, mean age 32.1+/-12.4 years) with suspected perimyocarditis (history of influenza, typical symptoms, ECG and echocardiographic results as well as myocardial necrotic markers). Plasma BNP was assessed at bedside at the time of admission.. Plasma BNP, measured in 12 patients, was 163+/-154 pg/mL (max. 519 pg/mL) and exceeded upper normal level in 6 (50%) patients. When normal levels were adjusted for age and gender, 9 (80%) patients had elevated BNP. One patient had heart failure symptoms and a BNP level of 205 pg/mL. In all 4 patients who had transient myocardial contractility disturbances, detected by echocardiography, BNP level exceeded 100 pg/mL.. BNP level is increased in some patients with acute perimyocarditis. BNP elevation is probably associated with hemodynamical stress caused by transient contractility abnormalities. Diagnostic and prognostic role of BNP in acute perimyocarditis requires further studies.

Topics: Adult; Biomarkers; Echocardiography; Electrocardiography; Female; Follow-Up Studies; Humans; Male; Myocarditis; Natriuretic Peptide, Brain; Predictive Value of Tests; Sensitivity and Specificity

Topics: Atrial Natriuretic Factor; Heart; Humans; Interferon-beta; Myocardial Infarction; Myocarditis; Natriuretic Peptide, Brain; Predictive Value of Tests; Risk Assessment; Stroke Volume

So as to determine the value of brain natriuretic peptide in the plasma as a biochemical marker for myocarditis of Kawasaki disease, we studied 69 patients. The blood samples, electrocardiograms and cross-sectional echocardiograms were obtained before the commencement of treatment and in the convalescent phase.. The mean concentration of brain natriuretic peptide in the plasma was 73.2 +/- 107.7 (mean +/- SD) pg/ml in the acute phase, and 7.9 +/- 7.5 pg/ml in the convalescent phase. We checked the electrocardiograms to find abnormal Q waves, elevation or depression of the ST segments, change in the pattern of the QRS complexes, and flattening or inversion of the T wave, all believed to be markers of myocarditis in Kawasaki disease. Those in whom the concentrations were greater than 50 pg/ml in the acute phase showed abnormal electrocardiograms more frequently than did those in whom the values were less than 50 pg/ml (21/29 vs 3/40, p < 0.0001 odds ratio 32.4). Amplitudes of the T wave in standard limb leads were measured both in the acute and convalescent phases, and the differences calculated. We regarded the sum total of these differences as representing "flattening T wave", and we named this variable as the total suppressed T wave voltage. We examined the correlation between the variable and the levels of brain natriuretic peptide in the plasma during the acute phase, demonstrating a significant correlation (r = 0.500, p < 0.0001). We conclude, therefore, that the concentration of brain natriuretic peptide measured in the plasma can be a useful biochemical marker for the myocarditis of Kawasaki disease. When the titer is over 50 pg/ml, the patient probably has an abnormal electrocardiogram and is most likely to have myocarditis.

Topics: Biomarkers; Chi-Square Distribution; Child; Child, Preschool; Cohort Studies; Echocardiography; Electrocardiography; Female; Humans; Infant; Male; Mucocutaneous Lymph Node Syndrome; Myocarditis; Natriuretic Peptide, Brain; Probability; Prognosis; Retrospective Studies; Sensitivity and Specificity; Severity of Illness Index

We analyzed the ventricular expression of atrial and brain natriuretic peptides (ANP and BNP) in patients with myocarditis. Immunohistochemical analysis of endomyocardial biopsy specimens showed ANP and BNP immunoreactivity in the early myocarditis group (ANP in 4/10 and BNP in 3/10) and the late myocarditis group (ANP and BNP in 4/10), but not in the controls (0/8). Hemodynamic parameters, such as left ventricular volume indexes, pulmonary capillary wedge pressure, and left ventricular end-diastolic pressure, were higher and the cardiac index and ejection fraction were lower in the patients positive for ANP and/or BNP. Histological changes, including myocyte size, cellular necrosis, inflammatory infiltrates and fibrosis, were more severe in the immunohistochemically positive biopsy specimens. In the autopsy hearts, ANP- or BNP-positive myocytes were noted in the chronic myocarditis or postmyocarditis group, but not in acute fulminant myocarditis or in normal controls. Both ANP and BNP were predominantly localized in the residual myocytes edging the myocardial lesions, and also in the myocytes just beneath the left ventricular endocardium. This study demonstrated augmented ventricular ANP and BNP expressions in patients with myocarditis, and suggested that regional stress is important in the augmentation of these peptides as well as hemodynamic stress.

Topics: Adolescent; Adult; Atrial Natriuretic Factor; Biopsy; Female; Follow-Up Studies; Heart Ventricles; Hemodynamics; Humans; Immunohistochemistry; Male; Middle Aged; Myocarditis; Natriuretic Peptide, Brain; Nerve Tissue Proteins